Hypercalcemia in Glucagon Cell Hyperplasia and Neoplasia (Mahvash Syndrome): A New Association

The Journal of Clinical Endocrinology and Metabolism
Matti L GildAnthony J Gill

Abstract

Hyperglucagonemia in the absence of glucagonomas is rare. Biallelic-inactivating mutations in the glucagon receptor gene (GCGR) cause glucagon cell hyperplasia and neoplasia (GCHN), also termed Mahvash syndrome. Here, we report the first case to our knowledge of GCHN presenting with hypercalcemia and demonstrate a unique relationship between calcium and α-cell hyperplasia. A 47-year-old man presented with severe PTH-independent hypercalcemia, 13.95 mg/dL (3.48 mmol/L). Imaging and extensive pathology tests yielded no conclusive cause. Glucagon levels >300 times the upper limit of normal were discovered. Subtotal pancreatectomy identified α-cell hyperplasia and neoplasia with metastatic disease in lymph nodes. Genomic analysis confirmed a homozygous missense variant in GCGR (Asp63Asn). This is a previously described pathologic variant and has a known association with GCHN. Inactivating mutations of the glucagon receptor gene lead to nonfunctional hyperglucagonemia and are associated with GCHN. Homozygous or compound heterozygous GCGR mutations are associated with α-cell hyperplasia, a known precursor to pancreatic neuroendocrine tumors that can metastasize. Hypercalcemia is an unreported consequence of GCHN with an unclear mecha...Continue Reading

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Citations

Jan 26, 2020·International Journal of Molecular Sciences·Qi KangMingyu Li
Aug 17, 2020·Radiographics : a Review Publication of the Radiological Society of North America, Inc·Lokesh KhannaVenkata S Katabathina
Jun 19, 2021·Radiographics : a Review Publication of the Radiological Society of North America, Inc·Venkata S KatabathinaSrinivasa R Prasad

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